Search PubMed⌕ Search

Biomedical subjects

Rebecca Smith

Publications and source records attributed to Rebecca Smith.

At least 19 recordsLinked to original sources
PubMed2024

DNA damage-induced EMT controlled by the PARP-dependent chromatin remodeler ALC1 promotes DNA repair efficiency through RAD51 in tumor cells.

Epithelial-to-mesenchymal transition (EMT) allows cancer cells to metastasize while acquiring resistance to apoptosis and chemotherapeutic agents with significant implications for patients' prognosis and survival. Despite its clinical relevance, the mechanisms initiating EMT during cancer progression remain poorly understood. We demonstrate that DNA damage triggers EMT and that activation of poly (ADP-ribose) polymerase (PARP) and the PARP-dependent chromatin remodeler ALC1 (CHD1L) was required for this response. Our results suggest that this activation directly facilitates access to the chromatin of EMT transcriptional factors (TFs) which then initiate cell reprogramming. We also show that EMT-TFs bind to the RAD51 promoter to stimulate its expression and to promote DNA repair by homologous recombination. Importantly, a clinically relevant PARP inhibitor reversed or prevented EMT in response to DNA damage while resensitizing tumor cells to other genotoxic agents. Overall, our observations shed light on the intricate relationship between EMT, DNA damage response, and PARP inhibitors, providing potential insights for in cancer therapeutics.

Humans↗
PubMed2006

Seat belt use among 13-15 year olds in primary and secondary enforcement law states.

CONTEXT: Coverage and enforcement provisions of safety belt use laws vary by state. Most laws cover drivers and passengers age 16 and above. "Primary" enforcement laws allow police to stop and ticket a motorist for a safety belt law violation. With "secondary" enforcement laws, ticketing can only occur in the presence of another traffic infraction. Given the lower rates of restraint use among teen drivers and their passengers, the effect of primary enforcement laws on the restraint use of young teen passengers is of particular interest. OBJECTIVE: To compare restraint use by 13-15 year olds passengers in motor vehicle crashes in states with primary versus secondary enforcement safety belt laws. METHODS: Cross-sectional study of 3953 crashes involving 5372 children, representing 54,226 children aged 13-15 years in 41,198 crashes of insured vehicles in 16 states and Washington, DC between December 1, 1998 and December 31, 2004, with data collected via insurance claims records and a telephone survey. RESULTS: Non-use of restraints by 13-15 year olds was 7.2% (95% CI 4.3-10.1%) greater in secondary enforcement states (10.8%) as compared to states with primary enforcement laws (3.6%). After controlling for driver's age and restraint status and the seating row of the occupant, a 13-15 year olds was over twice as likely to be unrestrained in a secondary enforcement state as compared to a primary enforcement state (adjusted RR=2.2, 95% CI 1.5-3.1). CONCLUSIONS: States considering primary enforcement provisions to their restraint laws should consider the potential benefits these laws may have to all occupants in the vehicle, particularly young adolescents who are nearing driving age.

Adolescent↗
PubMed2006

An interdisciplinary approach to introducing professionalism.

OBJECTIVE: To provide interdisciplinary structured activities in academic and clinical settings for introducing the concept of professionalism to health professions students. DESIGN: Undergraduate and graduate students from 8 health care disciplines including pharmacy, nursing, communication sciences and disorders, dietetics and nutrition science, genetic counseling, advanced medical imaging, medical technology, and physical therapy participated in an orientation program focusing on interdisciplinary health care and professionalism, as well as a field experience. ASSESSMENT: Survey results from both components (orientation, n = 284; field experience, n = 123) indicated that the project was valuable in increasing students' awareness of (1) the importance of professionalism in the clinical setting and (2) the potential contributions of their profession to the health care team. CONCLUSION: Health professions curricula should include interdisciplinary learning opportunities that enhance collaboration, collegiality, and professionalism among future members of the health care team.

Communication↗
PubMed2006

Cerebral cortical processing of swallowing in older adults.

While brain-imaging studies in young adults have implicated multiple cortical regions in swallowing, investigations in older subjects are lacking. This study examined the neural representations of voluntary saliva swallowing and water swallowing in older adults. Nine healthy females were examined with event-related functional magnetic resonance imaging (fMRI) while laryngeal swallow-related movements were recorded. Swallowing in the older adults, like young adults, activated multiple cortical regions, most prominently the lateral pericentral, perisylvian, and anterior cingulate cortex. Activation of the postcentral gyrus was lateralized to the left hemisphere for saliva and water swallowing, consistent with our findings in young female subjects. Comparison of saliva and water swallowing revealed a fourfold increase in the brain volume activated by the water swallow compared to the saliva swallow, particularly within the right premotor and prefrontal cortex. This task-specific activation pattern may represent a compensatory response to the demands of the water swallow in the face of age-related diminution of oral sensorimotor function.

Aged↗
PubMed2006

A novel strategy for the identification of genomic islands by comparative analysis of the contents and contexts of tRNA sites in closely related bacteria.

We devised software tools to systematically investigate the contents and contexts of bacterial tRNA and tmRNA genes, which are known insertion hotspots for genomic islands (GIs). The strategy, based on MAUVE-facilitated multigenome comparisons, was used to examine 87 Escherichia coli MG1655 tRNA and tmRNA genes and their orthologues in E.coli EDL933, E.coli CFT073 and Shigella flexneri Sf301. Our approach identified 49 GIs occupying approximately 1.7 Mb that mapped to 18 tRNA genes, missing 2 but identifying a further 30 GIs as compared with Islander [Y. Mantri and K. P. Williams (2004), Nucleic Acids Res., 32, D55-D58]. All these GIs had many strain-specific CDS, anomalous GC contents and/or significant dinucleotide biases, consistent with foreign origins. Our analysis demonstrated marked conservation of sequences flanking both empty tRNA sites and tRNA-associated GIs across all four genomes. Remarkably, there were only 2 upstream and 5 downstream deletions adjacent to the 328 loci investigated. In silico PCR analysis based on conserved flanking regions was also used to interrogate hotspots in another eight completely or partially sequenced E.coli and Shigella genomes. The tools developed are ideal for the analysis of other bacterial species and will lead to in silico and experimental discovery of new genomic islands.

Computational Biology↗
PubMed2006

Parent driver characteristics associated with sub-optimal restraint of child passengers.

OBJECTIVES: To identify parent driver demographic and socioeconomic characteristics associated with the use of sub-optimal restraints for child passengers under nine years. METHODS: Cross-sectional study using in-depth, validated telephone interviews with parent drivers in a probability sample of 3,818 vehicle crashes involving 5,146 children. Sub-optimal restraint was defined as use of forward-facing child safety seats for infants under one or weighing under 20 lbs, and any seat-belt use for children under 9. RESULTS: Sub-optimal restraint was more common among children under one and between four and eight years than among children aged one to three years (18%, 65%, and 5%, respectively). For children under nine, independent risk factors for sub-optimal restraint were: non-Hispanic black parent drivers (with non-Hispanic white parents as reference, adjusted relative risk, adjusted RR = 1.24, 95% CI: 1.09-1.41); less educated parents (with college graduate or above as reference: high school, adjusted RR = 1.27, 95% CI: 1.12-1.44; less than high school graduate, adjusted RR = 1.36, 95% CI: 1.13-1.63); and lower family income (with $50,000 or more as reference: <$20,000, adjusted RR = 1.23, 95% CI: 1.07-1.40). Multivariate analysis revealed the following independent risk factors for sub-optimal restraint among four-to-eight-year-olds: older parent age, limited education, black race, and income below $20,000. CONCLUSIONS: Parents with low educational levels or of non-Hispanic black background may require additional anticipatory guidance regarding child passenger safety. The importance of poverty in predicting sub-optimal restraint underscores the importance of child restraint and booster seat disbursement and education programs, potentially through Medicaid.

Accidents, Traffic↗
PubMed2006

A mental health program for ground zero rescue and recovery workers: cases and observations.

Clinical vignettes from the World Trade Center Worker and Volunteer Mental Health Monitoring and Treatment Program at the Mount Sinai Medical Center in New York City are presented. The hospital-based program pairs mental health screenings with federally funded occupational medical screenings to identify persons with mental health problems related to their rescue and recovery roles. The program also provides on-site mental health treatment. The cases illustrate the diverse mental health needs of the rescue and recovery workers, some of whom initially sought treatment years after September 11, 2001. The cases show that in addition to symptoms of posttraumatic stress disorder, workers experienced survivor guilt, distressing memories of childhood trauma, shame associated with intense feelings, substance abuse relapse, psychosis, and problems with family relationships.

Adult↗
PubMed2006

A worksite diabetes prevention program: two-year impact on employee health.

The purpose of this study was to determine the 2-year impact of a worksite-based diabetes prevention program. Thirty-seven pre-diabetic and previously undiagnosed diabetic employees participating in a 12-month worksite diabetes prevention program were included. Weight, body mass index, waist circumference, oral glucose tolerance testing, fasting insulin, blood lipids, and aerobic fitness had improved significantly after 6 months. Much of this improvement continued through 12 months. One year following the intervention, oral glucose tolerance and aerobic fitness had improved significantly. Of the 22 employees remaining in the study through 24 months, more than half had normal results on glucose tolerance testing. Worksite diabetes prevention programs may reduce blood glucose below pre-diabetic and diabetic levels. Improvements in diabetes risk factors persisted for at least 2 years in most of these employees.

Blood Glucose↗
PubMed2006

Global veterinary opportunities and responsibilities: some recent graduates' perspectives.

The veterinary profession has critical global responsibilities. To help meet these responsibilities, it is critical that the training programs for veterinary graduates provide them with the skills, knowledge, understanding, and professional attributes pertinent to meeting these responsibilities. The programs at US veterinary schools, in the full range from admissions, to curriculum, to post-graduate opportunities, fall short in many critical arenas.

Animals↗
PubMed2005

The genetic portrait of an outbreak strain.

Unique events in the genome of Mycobacterium tuberculosis, including deletions and IS6110 insertions, have been proposed to be responsible for the virulence phenotype of outbreak strains. Based on this premise, we determined ten IS6110 insertion sites in the genome of the M. tuberculosis CH strain, which was responsible for a large outbreak in Leicestershire, England. Together with previous data on genomic deletions, it was found that 16 genes were mutated either by IS6110 insertions or deletions. The likely impact of these genomic events on the phenotype of the CH strain is discussed.

Disease Outbreaks↗
PubMed2005

ArrayOme: a program for estimating the sizes of microarray-visualized bacterial genomes.

ArrayOme is a new program that calculates the size of genomes represented by microarray-based probes and facilitates recognition of key bacterial strains carrying large numbers of novel genes. Protein-coding sequences (CDS) that are contiguous on annotated reference templates and classified as 'Present' in the test strain by hybridization to microarrays are merged into ICs (ICs). These ICs are then extended to account for flanking intergenic sequences. Finally, the lengths of all extended ICs are summated to yield the 'microarray-visualized genome (MVG)' size. We tested and validated ArrayOme using both experimental and in silico-generated genomic hybridization data. MVG sizing of five sequenced Escherichia coli and Shigella strains resulted in an accuracy of 97-99%, as compared to true genome sizes, when the comprehensive ShE.coli meta-array gene sequences (6239 CDS) were used for in silico hybridization analysis. However, the E.coli CFT073 genome size was underestimated by 14% as this meta-array lacked probes for many CFT073 CDS. ArrayOme permits rapid recognition of discordances between PFGE-measured genome and MVG sizes, thereby enabling high-throughput identification of strains rich in novel genes. Gene discovery studies focused on these strains will greatly facilitate characterization of the global gene pool accessible to individual bacterial species.

Computational Biology↗
PubMed2005

Effects of seating position and appropriate restraint use on the risk of injury to children in motor vehicle crashes.

BACKGROUND: Currently, many states are upgrading their child restraint laws to include provisions for the use of age-appropriate restraints through 6 to 8 years of age, with some also requiring rear seating for children, enabling the laws to be in closer alignment with best-practice recommendations. OBJECTIVE: To evaluate the relationships of seating position and restraint status to the risk of injury among children in passenger vehicle crashes. METHODS: This was a cross-sectional study of children <16 years of age who were involved in crashes of insured vehicles in 15 states, with data collected via insurance claims records and a telephone survey. A probability sample of 17980 children in 11506 crashes, representing 229106 children in 146613 crashes, was collected between December 1, 1998, and November 30, 2002. Parent reports were used to define restraint status, seating position, and occurrence of clinically significant injuries, with the use of a previously validated instrument. RESULTS: Approximately 62% of the children used seat belts, 35% used child restraints, and 3% used no restraint. Nearly 4 of 5 children sat in the rear seat, with one half of all children being restrained appropriately for their age in the rear, although this varied according to the age of the child. Overall, 1.6% of children suffered serious injuries, 13.5% had minor injuries, and 84.9% did not have any injury. Unrestrained children in the front were at the highest risk of injury and appropriately restrained children in the rear were at the lowest risk, for all age groups. Inappropriately restrained children were at nearly twice the risk of injury, compared with appropriately restrained children (odds ratio [OR]: 1.8; 95% confidence interval [CI]: 1.4-2.3), whereas unrestrained children were at >3 times the risk (OR: 3.2; 95% CI: 2.5-4.1). The effect of seating row was smaller than the effect of restraint status; children in the front seat were at 40% greater risk of injury, compared with children in the rear seat (OR: 1.4; 95% CI: 1.2-1.7). Had all children in the study population been appropriately restrained in the rear seat, 1014 serious injuries (95% CI: 675-1353 injuries) would have been prevented (with the assumption that restraint effectiveness does not depend on a variety of other driver-related, child-related, crash-related, vehicle-related, and environmental factors). CONCLUSIONS: Age-appropriate restraint confers relatively more safety benefit than rear seating, but the 2 work synergistically to provide the best protection for children in crashes. These results support the current focus on age-appropriate restraint in recently upgraded state child restraint laws. However, it is important to note that considerable added benefit would be realized with additional requirements for rear seating.

Accidents, Traffic↗
PubMed2005

The diabetes prevention program: a worksite experience.

The purpose of this study was to determine if the U.S. National Institutes of Health Diabetes Prevention Program (DPP) could be successfully implemented in a worksite setting. Thirty-seven adult employees of BD Medical Systems of Sandy, Utah were enrolled in a single-group time-series study using the DPP. Two-hour oral glucose tolerance tests (OGTT) and other outcomes were measured at baseline, 6 months, and 12 months. Weight, body mass index, waist circumference, 2-hour OGTT, very low density lipoproteins, triglycerides, and aerobic fitness were significantly improved at 6 and 12 months and showed overall significant improvement across time. Fasting blood insulin, total cholesterol, low density lipoproteins, and total cholesterol/high density lipoproteins ratio were significantly improved at 6 months, but not at 12 months. Eighteen of the program participants (51%) were no longer in the pre-diabetes and diabetes categories after 1 year. Existing worksite health promotion and occupational health professionals can successfully offer the DPP and help employees improve glucose tolerance.

Analysis of Variance↗
PubMed2004

Trends of behavioral risk factors in motor vehicle crashes in Utah, 1992-1997.

OBJECTIVE: Measure changes in the prevalence of behavioral factors including police-reported fatigue and alcohol intoxication, as well as self-reported seatbelt use, and assess their effect on hospitalization or death after a motor vehicle crash. METHODS: Probabilistic linkage was used to match drivers in motor vehicle crashes with hospital discharge records for the years 1992-1997. Frequencies of specific behavioral factors were evaluated using the Cochran-Armitage test for trend. Odds ratios and corresponding 95% confidence intervals were calculated using generalized estimating equations (GEEs) with crash and driver characteristics as independent variables and hospitalization or death as the dependent variable. RESULTS: The analysis database consisted of 450,286 crash driver records, which linked to 4219 (0.9%) hospitalizations or deaths. There was an increasing trend for self-reported seatbelt use among crash-involved drivers from 80.5% in 1992 to 89.3% in 1997 (P<0.001). Police-reported alcohol intoxication among crash-involved drivers showed a decreasing trend from 2.4% in 1992 to 1.5% in 1997 (P<0.001). There was no trend for police-reported fatigue-related crashes. Odds ratios of hospitalization or death for seatbelt use, alcohol involvement, and fatigue were significant and did not fluctuate considerably between 1992 and 1997. Seatbelt use offered a protective effect from hospitalization or death, while alcohol intoxication and fatigue contributed to increased likelihood of hospitalization or death. CONCLUSIONS: These results suggest that while some improvement has been made in decreasing seatbelt non-use and driver alcohol intoxication among crash-involved drivers, no improvement has been made in reducing fatigue-related crashes.

Accidents, Traffic↗
PubMed2003

Improvement in diastolic intraventricular pressure gradients in patients with HOCM after ethanol septal reduction.

We sought to validate measurement of intraventricular pressure gradients (IVPG) and analyze their change in patients with hypertrophic obstructive cardiomyopathy (HOCM) after ethanol septal reduction (ESR). Quantitative analysis of color M-mode Doppler (CMM) images may be used to estimate diastolic IVPG noninvasively. Noninvasive IVPG measurement was validated in 10 patients undergoing surgical myectomy. Echocardiograms were then analyzed in 19 patients at baseline and after ESR. Pulsed Doppler data through the mitral valve and pulmonary venous flow were obtained. CMM was used to obtain the flow propagation velocity (Vp) and to calculate IVPG off-line. Left atrial pressure was estimated with the use of previously validated Doppler equations. Data were compared before and after ESR. CMM-derived IVPG correlated well with invasive measurements obtained before and after surgical myectomy [r = 0.8, P < 0.01, Delta(CMM - invasive IVPG) = 0.09 +/- 0.45 mmHg]. ESR resulted in a decrease of resting LVOT systolic gradient from 62 +/- 10 to 29 +/- 5 mmHg (P < 0.001). There was a significant increase in the Vp and IVPG (from 48 +/- 5to 74 +/- 7 cm/s and from 1.5 +/- 0.2 to 2.6 +/- 0.3 mmHg, respectively, P < 0.001 for both). Estimated left atrial pressure decreased from 16.2 +/- 1.1 to 11.5 +/- 0.9 mmHg (P < 0.001). The increase in IVPG correlated with the reduction in the LVOT gradient (r = 0.6, P < 0.01). Reduction of LVOT obstruction after ESR is associated with an improvement in diastolic suction force. Noninvasive measurements of IVPG may be used as an indicator of diastolic function improvement in HOCM.

Cardiomyopathy, Hypertrophic↗
PubMed2003

Analysis of normal discourse patterns.

Twenty-five normal young adult college students provided speaking and writing samples using two elicitation procedures: picture description and personal narrative. Patterns of productivity, efficiency, and coherence were investigated while considering the demands imposed by mode of expression, task elicitation, cognitive distance, and verbal working memory. Samples were divided into top (S1) and bottom (S2) halves. Within group (S1/S2) and between group (pictured activity description/personal narrative) comparisons were made for oral vs. written samples, and performance measures were correlated with verbal working memory scores. Results indicated that the productivity measure was influenced by the type of elicitation task and was not related to verbal working memory scores. Efficiency was influenced by mode of expression and demonstrated a low correlation with verbal working memory scores. Coherence ratings were not influenced by type of elicitation task, mode of expression, or length of sample, and were not related to verbal working memory scores. Results are discussed in terms of the clinical utility of these discourse measures.

Adolescent↗
PubMed2003

Protein kinase C-dependent activation of the tumor necrosis factor receptor-mediated extrinsic cell death pathway underlies enhanced apoptosis in human myeloid leukemia cells exposed to bryostatin 1 and flavopiridol.

Interactions between the protein kinase C activator bryostatin 1 and the cyclin-dependent kinase (CDK) inhibitor flavopiridol (FP) have been examined in human myeloid leukemia cells (U937 and HL-60). Previous studies have demonstrated synergistic induction of apoptosis in leukemic cells exposed to the potent differentiation-inducer phorbol 12-myristate 13-acetate (PMA) in conjunction with FP [L. Cartee et al., Cancer Res., 61: 2583-2591, 2001]. Although bryostatin 1 (10 nM) is a very weak inducer of differentiation compared with PMA in these cells, coadministration of a minimally toxic concentration of FP (100 nM) did not promote bryostatin 1-related maturation but instead caused a marked increase in mitochondrial damage (e.g., cytochrome c release; loss of Deltapsi(m)), caspase activation, poly(ADP-ribose) polymerase cleavage, and apoptosis. Bryostatin 1/FP-induced apoptosis was significantly diminished in cells ectopically expressing dominant-negative Fas-associated death domain or by coadministration of tumor necrosis factor (TNF)-alpha soluble receptors, implicating the extrinsic pathway in bryostatin 1/FP actions. Enhanced apoptosis in bryostatin 1/FP-treated cells was accompanied by down-regulation of Mcl-1 and a sustained increase in TNF-alpha release. The selective protein kinase C inhibitor GFX blocked TNF-alpha and cytochrome c release in bryostatin 1/FP-treated cells and attenuated apoptosis. Finally, coadministration of bryostatin 1 (or PMA) with FP induced a marked increase in apoptosis in U937 cells ectopically expressing an NH(2)-terminal phosphorylation loop-deleted Bcl-2 protein, which are otherwise highly resistant to FP-mediated lethality. Taken together, these findings suggest that synergistic induction of apoptosis by bryostatin 1 and FP does not stem from disruption of the leukemic cell maturation process but instead results from enhanced release of TNF-alpha and activation of the extrinsic apoptotic cascade, culminating in cell death.

Antineoplastic Agents↗